Ratiometric Molecular Sensor for Monitoring Oxygen Levels in Living Cells

Yoshihara, Toshitada; Yamaguchi, Yuji; Hosaka, Masahiro; Takeuchi, Toshiyuki; Tobita, Seiji

doi:10.1002/ange.201107557

Cited by 43 publications

(24 citation statements)

References 28 publications

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“…As noted in the introduction, the longlived triplet states of transition metal complexes are often efficiently quenched by O 2 . Ruthenium(II) complexes have been the subject of most investigation to date [58][59][60], but any phosphorescent transition metal complex is a potential oxygen sensor, including platinum(II), palladium(II) and iridium(III) complexes [61][62][63].…”

Section: From Gating Out Autofluorescence To Determining Intracellulamentioning

confidence: 99%

Time-Resolved Emission Imaging Microscopy Using Phosphorescent Metal Complexes: Taking FLIM and PLIM to New Lengths

Baggaley

Weinstein

Williams

2014

Luminescent and Photoactive Transition Metal Complexes as Biomolecular Probes and Cellular Reagents

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Luminescent metal complexes are increasingly being investigated as emissive probes and sensors for cell imaging using what is traditionally termed fluorescence microscopy. The nature of the emission in the case of second-and third-row metal complexes is phosphorescence rather than fluorescence, as it emanates from triplet rather than singlet excited states, but the usual terminology overlooks the distinction between the quantum mechanical origins of the processes. In steady-state imaging, such metal complexes may be alternatives to widely used fluorescent organic molecules, used in exactly the same way but offering advantages such as ease of synthesis and colour tuning. However, there is a striking difference compared to fluorescent organic molecules, namely the much longer lifetime of phosphorescence compared to fluorescence. Phosphorescence lifetimes of metal complexes are typically around a microsecond compared to the nanosecond values found for fluorescence of organic molecules. In this contribution, we will discuss how these long lifetimes can be put to practical use. Applications such as time-gated imaging allow discrimination from background fluorescence in cells and tissues, while increased sensitivity to quenchers provides a means of designing more responsive probes, for example, for oxygen. We also describe how the technique of fluorescence lifetime imaging microscopy (FLIM) -which provides images based on lifetimes at different points in the image -can be extended from the usual nanosecond range to microseconds. Key developments in instrumentation as well as the properties of complexes suitable for the purpose are discussed, including the use of two-photon excitation methods. A number of different research groups have made pioneering contributions to the instrumental set-ups, but the E. Baggaley and J.A. Weinstein Department of Chemistry, University of Sheffield, Sheffield S3 7HF, UK e-mail: liz.baggaley@sheffield.ac.uk; julia.weinstein@sheffield.ac.uk J.A.G. Williams (*) Department of Chemistry, Durham University, Durham DH1 3LE, UK e-mail: j.a.g.williams@durham.ac.uk terminology and acronyms have not developed in a systematic way. We review the distinction between time-gating (to eliminate background emission) and true timeresolved imaging (whereby decay kinetics at each point in an image are monitored). For instance, terms such as PLIM (phosphorescence lifetime imaging microscopy) and TRLM (time-resolved luminescence microscopy) refer essentially to the same technique, whilst TREM (time-resolved emission imaging microscopy) embraces these long timescale methods as well as the more well-established technique of FLIM.Keywords Cell imaging Á Fluorescence Á Fluorescence lifetime imaging microscopy Á Imaging Á Iridium Á Metal complex Á Microscopy Á Oxygen sensing Á Phosphorescence Á Phosphorescence lifetime imaging microscopy Á Platinum Á Ruthenium Á Time-resolved emission imaging microscopy Á Time-resolved fluorescence Á Time-resolved luminescence microscopy Á Tissue imaging

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Section: From Gating Out Autofluorescence To Determining Intracellulamentioning

confidence: 99%

Time-Resolved Emission Imaging Microscopy Using Phosphorescent Metal Complexes: Taking FLIM and PLIM to New Lengths

Baggaley

Weinstein

Williams

2014

Luminescent and Photoactive Transition Metal Complexes as Biomolecular Probes and Cellular Reagents

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“…All of these limitations compromise the ability of these probes to detect hypoxia in the tumour. On the other hand, phosphorescent transition metal complexes have shown to be very effective in imaging and sensing the oxygen level in biological samples 19,20 , given the high sensitivity to oxygen, tunable excitation and emission wavelength and high luminescent quantum yields 21,22 . However, the phosphorescent transition metal imaging probes have poor biodistribution and pharmacokinetic profiles for tumour imaging due to nonspecific uptake by normal tissues, binding to plasma proteins and rapid renal clearance, limiting their ability to differentiate hypoxic and normoxic conditions 23 .…”

mentioning

confidence: 99%

Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo

et al. 2015

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Highly sensitive and specific non-invasive molecular imaging methods are particularly desirable for the early detection of cancers. Here we report a near-infrared optical imaging probe highly specific to the hypoxic tumour microenvironment to detect tumour and cancer cells with the sensitivity to a few thousands cancer cells. This oxygen-sensitive, near-infrared emitting and water-soluble phosphorescent macromolecular probe can not only report the hypoxic tumour environment of various cancer models, including metastatic tumours in vivo, but can also detect a small amount of cancer cells before the formation of the tumour based on the increased oxygen consumption during cancer cell proliferation. Thus, the reported hypoxia-sensitive probe may offer an imaging tool for characterizing the tumour microenvironment in vivo, detecting cancer cells at a very early stage of tumour development and lymph node metastasis.

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“…This is usually done by using bandpass filters or, alternatively, by attributing the emissions of the components to different color channels of an RGB camera [128,212,228]. A more elegant solution is an application of tailor-made indicators which possess dual emission (oxygen-sensitive phosphorescence and oxygen-insensitive fluorescence) but very few examples have been reported so far [244,254,256,258].…”

Section: Sensing Methodologiesmentioning

confidence: 99%

“…Very recently, Yoshihara et al [254] presented a novel intrinsic ratiometric molecular probe, the C343-Pro 4 -BTP 79 ( Fig. 13) which consists of an oxygen-sensitive phosphor (Ir(III)BTP, BTP0bis(2-(2′-benzothienyl)-pyridinato-N,C 3 )) connected to an oxygen-insensitive fluorophore (coumarin C343) by a tetraproline linker.…”

Section: −1mentioning

confidence: 99%

Indicators for optical oxygen sensors

Borisov¹,

Quaranta²,

Klimant³

2012

Advances in Chemical Bioanalysis

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Continuous monitoring of oxygen concentration is of great importance in many different areas of research which range from medical applications to food packaging. In the last three decades, significant progress has been made in the field of optical sensing technology and this review will highlight the one inherent to the development of oxygen indicators. The first section outlines the bioanalytical fields in which optical oxygen sensors have been applied. The second section gives the reader a comprehensive summary of the existing oxygen indicators with a critical highlight on their photophysical and sensing properties. Altogether, this review is meant to give the potential user a guide to select the most suitable oxygen indicator for the particular application of interest.

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Ratiometric Molecular Sensor for Monitoring Oxygen Levels in Living Cells

Cited by 43 publications

References 28 publications

Time-Resolved Emission Imaging Microscopy Using Phosphorescent Metal Complexes: Taking FLIM and PLIM to New Lengths

Time-Resolved Emission Imaging Microscopy Using Phosphorescent Metal Complexes: Taking FLIM and PLIM to New Lengths

Hypoxia-specific ultrasensitive detection of tumours and cancer cells in vivo

Indicators for optical oxygen sensors

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